Exploring the Cause of Survival Disparities in EGFR-mutated Lung Cancer Subtypes: Unraveling Distinctive Genomic and Phenotypic Features of 19Del and L858R Mutation Subtypes

Abstract

Abstract Differences in the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have been observed between lung cancer patients with 19 exon deletion (19Del) and L858R mutation. We investigate the multi-omics information from the TCGA LUAD dataset and validate it using the GEO (GSE190139, GSE147377) and MSK datasets. Somatic loss-of-function alteration of RBM10 and altered Immune infiltration profile correlated with L858R decreased survival. Meanwhile, in the L858R mutation group, 9p21.3 loss and CDKN2B methylation, increased cell cycle-related gene expression, and the enrichment in cell cycle pathways were associated with poor survival. Comprehensive genomic and phenotypic analysis of the EGFR-mutated lung cancer subtypes reveals distinctive features of each subtype, laying the groundwork for subtype-specific treatment and care options for lung cancer patients.